We propose to investigate how an Interleukin 1-containing supernate, derived from the macrophage cell line P388D1 after stimulation with phorbol myristic acetate, regulates the function of certain cloned T cell populations which are cytolytic and/or secrete lymphokines. We have obtained evidence that the macrophage supernatant, which is devoid of Interleukin 2 activity, fails to induce the proliferation of cloned helper cells and of conventional cloned cytolytic cells. However, the macrophage supernatant potentiates the proliferative response of certain H-2 restricted cytolytic clones to appropriate alloantigens, and causes these clones to lose cytolytic activity. The clones which respond to the macrophage supernatant may belong to the newly described class of cytolytic cells, the helper-independent cytolytic T cell, since they do not require exogenous growth factors for a proliferative response to alloantigens. This is not characteristic of conventional T cell clones. Our studies suggest the existence of a previously unknown macrophage-T cell regulatory interaction. Since helper-independent cytolytic T cells can secrete mitogenic lymphokines, our studies may also suggest an alternative mechanism by which Interleukin I can influence the production of Interleukin 2-like biological activity. We propose to determine i) if Interleukin 1, or another molecular component of the macrophage supernatant, is responsible for these biological activities on cloned T cells, ii) how the macrophage supernatant cooperates with stimulator cells to cause clonal proliferation, iii) if the macrophage supernatant influences lymphokine secretion by cloned cells, iv) how the macrophage supernatant interferes with clone cytolytic activity, and v) if the loss of cytolytic activity following contact with the macrophage supernatant is reversible, and if it is accompanied by alterations in the display of certain characteristic cell surface proteins. Thus, using purified macrophage products and cloned T cell populations we will probe some of the lymphokine-mediated mechanisms by which macrophages influence the function of various T cell populations.